Pyrazol-4-yl carboxamide derivatives as microbiocides

ABSTRACT

Compounds of formula (I) wherein R 1  is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy; R 2  is C 1 -C 4 alkyl; R 3  is hydrogen or halogen; R 4  is hydrogen, C 1 -C 4 alkyl or C 1 -C 4 halogenalkyl; R 5  is hydrogen, halogen or C 1 -C 4 alkyl; R 6  is hydrogen, halogen, C 1 -C 4 alkyl, C 2 -C 6 alkenyl or C 3 -C 6 alkynyl; R 7  is hydrogen, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl-C 3 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 6 haloalkenyl, or C 2 -C 6 haloalkenyloxy; R 5  is hydrogen, halogen, C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, amino, C 1 -C 6 alkylcarbonylamino, C 1 -C 6 alkoxycarbonylamino or C 3 -C 6 cycloalkylcarbonylamino; R 9  is hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl-C 3 -C 6 alkynyl, halophenoxy, halophenyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 6 haloalkenyl, or C 2 -C 6 haloalkenyloxy; R 10  is hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl or C 3 -C 6 alkynyl; X is CH 2 , O or S; n is 0, 1 or 2; and agronomically acceptable salts/isomers/structural isomers/stereoisomers/diastereoisomers/enantiomers/tautomers and N-oxides of those compounds, are suitable for use as microbiocides.

The present invention relates to novel microbiocidally active, inparticular fungicidally active, carboxamides. It further relates tointermediates used in the preparation of these compounds, tocompositions which comprise these compounds and to their use inagriculture or horticulture for controlling or preventing infestation ofplants by phytopathogenic microorganisms, preferably fungi.

Fungicidally active N-substituted-N-bicyclic carboxamides are described,for example, in WO 2009/016218 and WO 2010/130767. It has been foundthat novel carboxamides with a specific substitution pattern havemicrobiocidal activity.

The present invention accordingly relates to N-alkoxycarboxamides offormula I

whereinR₁ is C₁-C₄alkyl, C₁-C₄haloalkyl or C₁-C₄alkoxy;R₂ is C₁-C₄alkyl;R₃ is hydrogen or halogen;R₄ is hydrogen, C₁-C₄alkyl or C₁-C₄halogenalkyl;R₅ is hydrogen, halogen or C₁-C₄alkyl;R₆ is hydrogen, halogen, C₁-C₄alkyl, C₂-C₆alkenyl or C₃-C₆alkynyl;R₇ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl,C₃-C₆alkynyl, C₃-C₆cycloalkyl-C₃-C₆alkynyl, C₁-C₆haloalkyl,C₁-C₆haloalkoxy, C₂-C₆haloalkenyl, or C₂-C₆haloalkenyloxy;R₈ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl,C₃-C₆alkynyl, amino, C₁-C₆alkylcarbonylamino, C₁-C₆alkoxycarbonylaminoor C₃-C₆cycloalkylcarbonylamino;R₉ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl,C₃-C₆alkynyl, C₃-C₆cycloalkyl-C₃-C₆alkynyl, halophenoxy, halophenyl,C₁-C₆haloalkyl, C₁-C₆haloalkoxy, C₂-C₆haloalkenyl, orC₂-C₆haloalkenyloxy;R₁₀ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl orC₃-C₆alkynyl;

X is CH₂, O or S;

n is 0, 1 or 2; and agronomically acceptable salts/isomers/structuralisomers/stereoisomers/diastereoisomers/enantiomers/tautomers andN-oxides of those compounds.

The alkyl groups occurring in the definitions of the substituents can bestraight-chain or branched and are, for example, methyl, ethyl,n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl,iso-butyl or tert-butyl. Alkoxy, alkenyl and alkynyl radicals arederived from the alkyl radicals mentioned. The alkenyl and alkynylgroups can be mono- or di-unsaturated. The cycloalkyl groups occurringin the definitions of the substituents are, for example, cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl. Halogen is generally fluorine,chlorine, bromine or iodine, preferably fluorine, bromine or chlorine.This also applies, correspondingly, to halogen in combination with othermeanings, such as halogenalkyl or halogenalkoxy. Haloalkyl groupspreferably have a chain length of from 1 to 4 carbon atoms. Halonalkylis, for example, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl,2-fluoroethyl, 2-chloroethyl, pentafluoroethyl,1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl,difluoromethyl, trifluoromethyl and dichlorofluoromethyl. Alkoxy is, forexample, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy,sec-butoxy and tert-butoxy; preferably methoxy and ethoxy. Halogenalkoxyis, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy,2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy,2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferablydifluoromethoxy, 2-chloroethoxy and trifluoromethoxy.C₁-C₆alkylcarbonylamino is, for example methylcarbonylamino(—NHC(O)CH₃), C₁-C₆alkoxycarbonylamino is for exampletert.butoxycarbonylamino (—NHC(O)O-tert.butyl) andC₃-C₆cycloalkylcarbonylamino is for example cyclopropylcarbonylamino(—NHC(O)-c-propyl).

In preferred compounds of formula I, independently from each other,

a) R₁ is difluoromethyl, trifluoromethyl or methyl,b) R₂ is methyl;c) R₃ is hydrogen;d) R₄ is hydrogen, methyl or ethyl;e) R₅ is hydrogen, fluoro or methyl;f) R₆ is hydrogen;g) n is 1 or 2;

h) X is CH₂;

i) R₇, R₈, R₉ and R₁₀ are hydrogen or chloro;j) R₉ is chloro, bromo or C₁-C₄alkyl.

Especially preferred compounds of formula I are those, wherein

R₁ is difluoromethyl or trifluoromethyl;

R₂ is methyl;

R₃ is hydrogen;R₄ is methyl;R₆ is hydrogen, halogen, C₁-C₄alkyl, C₂-C₆alkenyl or C₃-C₆alkynyl;especially hydrogen; and R₇, R₈, R₉ and R₁₀ are, independently from eachother, hydrogen or halogen, preferably hydrogen or chloro.

Further compounds of formula I are preferred, wherein

R₆ is hydrogen.

In an especially preferred group of compounds of formula I,

R₁ is difluoromethyl, trifluoromethyl or methyl, especiallydifluoromethyl or trifluoromethyl;R₂ is methyl;R₃ is hydrogen;R₄ is methyl;R₅ is hydrogen fluoro or methyl; preferably hydrogen or fluoro;R₆ is hydrogen, halogen, C₁-C₄alkyl, C₂-C₆alkenyl or C₃-C₆alkynyl;n is 2;

X is CH₂; and

R₇, R₈, R₉ and R₁₀ are, independently from each other, hydrogen orhalogen, preferably hydrogen or chloro. In said especially preferredgroup of compounds of formula I, R₆ is preferably hydrogen.

In another preferred group of compounds of formula I,

R₁ is C₁-C₄haloalkyl;R₂ is C₁-C₄alkyl;R₃ is hydrogen;R₄ is C₁-C₄alkyl;R₅ is hydrogen or C₁-C₄alkyl;R₆ is hydrogen or C₁-C₄alkyl;R₇ is hydrogen;R₈ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₆alkoxy, amino,C₁-C₆alkylcarbonylamino, C₁-C₆alkoxycarbonylamino orC₃-C₆cycloalkylcarbonylamino;R₉ is hydrogen, halogen or C₁-C₆alkoxy;R₁₀ is hydrogen, halogen or C₁-C₆alkoxy;

X is CH₂, O or S; and

n is 1 or 2.

Compounds of formula I may be prepared by reacting a compound of formulaII

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, n and X are as defined underformula I; with a compound of formula III

in which R₁, R₂ and R₃ are as defined under formula I, and R* ishalogen, hydroxy or C₁₋₆ alkoxy, preferably chloro. Compounds of formulaIII are known and described, for example, in U.S. Pat. No. 5,093,347 andWO 2008/148570 or can be prepared by methods known in the art. Forexample, the compound of formula IIIa

wherein R₉ is C₁-C₆alkyl, can be prepared by reacting a compound offormula IIIb

wherein R₉ is as defined for formula IIIa and R₁₀ is C₁-C₆alkyl, withmethylhydrazine in the presence of water, a hydroxide base and anorganic solvent selected from an aromatic hydrocarbon and ahalogen-substituted aromatic hydrocarbon.

The reactions for the preparation of compounds of formula I areadvantageously carried out in aprotic inert organic solvents. Suchsolvents are hydrocarbons such as benzene, toluene, xylene orcyclohexane, chlorinated hydrocarbons such as dichloromethane,trichloromethane, tetrachloromethane or chlorobenzene, ethers such asdiethyl ether, ethylene glycol dimethyl ether, diethylene glycoldimethyl ether, tetrahydrofuran or dioxane, nitriles such asacetonitrile or propionitrile, amides such as N,N-dimethylformamide,diethylformamide or N-methylpyrrolidinone. The reaction temperatures areadvantageously between −20° C. and +120° C. In general, the reactionsare slightly exothermic and, as a rule, they can be carried out atambient temperature. To shorten the reaction time, or else to start thereaction, the mixture may be heated briefly to the boiling point of thereaction mixture. The reaction times can also be shortened by adding afew drops of base as reaction catalyst. Suitable bases are, inparticular, tertiary amines such as trimethylamine, triethylamine,quinuclidine, 1,4-diazabicyclo[2.2.2]octane,1,5-diazabicyclo[4.3.0]non-5-ene or 1,5-diazabicyclo[5.4.0]undec-7-ene.However, inorganic bases such as hydrides, e.g. sodium hydride orcalcium hydride, hydroxides, e.g. sodium hydroxide or potassiumhydroxide, carbonates such as sodium carbonate and potassium carbonate,or hydrogen carbonates such as potassium hydrogen carbonate and sodiumhydrogen carbonate may also be used as bases. The bases can be used assuch or else with catalytic amounts of a phase-transfer catalyst, forexample a crown ether, in particular 18-crown-6, or a tetraalkylammoniumsalt.

When R* is hydroxy, a coupling agent, such asbenzotriazol-1-yloxytris(dimethylamino) phosphoniumhexafluorophosphate,bis-(2-oxo-3-oxazolidinyl)-phosphinic acid chloride (BOP—Cl),N,N′-dicyclohexylcarbodiimide (DCC) or 1,1′-carbonyl-diimidazole (CDI),may be used.

The intermediates of formula II

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, n and X are as defined underformula I, preferably wherein R₄ is C₁-C₄alkyl; are novel and weredeveloped specifically for the preparation of the compounds of theformula I. Accordingly, these intermediates of the formula II also forma part of the subject-matter of the present invention.

The preferred substituent definitions for the compounds of formula I arealso valid for the compound of formula II. Thus, for example, preferredcompounds of formula II are those, wherein, independently from eachother,

a) R₄ is methyl;b) R₅ is hydrogen, fluoro or methyl;c) R₆ is hydrogen;d) n is 1 or 2;

e) X is CH₂;

f) R₇, R₈, R₉ and R₁₀ are hydrogen, chloro, bromo or C₁-C₄alkyl.

Intermediates of Formula IIA

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and n are as defined under formulaI, may be prepared as described in reaction scheme 1.

O-alkoxy oxime derivatives of formula VIa, in which R₄, R₅, R₆, R₇, R₈,R₉, R₁₀ and n are as defined under formula IIA, may be prepared bycondensation of ketone derivatives of formula IVa with O-alkylhydroxylamine derivatives of formula V or a salt thereof. Suitablesolvents carrying out the oximation step are hydrocarbons such asbenzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons suchas dichloromethane, trichloromethane, tetrachloromethane orchlorobenzene, ethers such as diethyl ether, ethylene glycol dimethylether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane,nitriles such as acetonitrile or propionitrile, amides such asN,N-dimethylformamide, diethylformamide, N-methylpyrrolidinone water ormixtures. The reaction temperatures are advantageously between −20° C.and +120° C. In general, the reactions can be carried out at ambienttemperature. Suitable bases are, in particular pyridine, tertiary aminessuch as trimethylamine, triethylamine, quinuclidine,1,4-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene or1,5-diazabicyclo[5.4.0]undec-7-ene. However, inorganic bases such ashydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g.sodium hydroxide or potassium hydroxide, carbonates such as sodiumcarbonate and potassium carbonate, or hydrogen carbonates such aspotassium hydrogen carbonate and sodium hydrogen carbonate may also beused as bases.

Alternatively O-alkoxy oxime derivatives of formula VIa may also beprepared by alkylation of oxime derivatives of formula VIa′ with acompound R₄—Y, in which R₄ is as defined under formula IIA and Yrepresents a leaving group, such as halogen, mesylate or tosylate, inthe presence of a base.

O-Alkylhydroxylamines of formula IIA may be prepared by the reduction ofO-alkoxy oxime derivatives of formula VI. It will be appreciated bythose skilled in the art that this reduction can be carried out with anumber of different reducing agents.

Intermediates of the Formula IVA

wherein R₅, R₆, R₇, R₈, R₉, R₁₀ are as defined under formula I, areknown and/or commercially available.

Intermediates of the Formula IVB

wherein R₅, R₆, R₇, R₈, R₉, R₁₀ are as defined under formula I, areknown or may be prepared in analogy to known procedures.

The compounds I and, where appropriate, the tautomers thereof, can, ifappropriate, also be obtained in the form of hydrates and/or includeother solvents, for example those which may have been used for thecrystallization of compounds which are present in solid form.

It has now been found that the compounds of formula I according to theinvention have, for practical purposes, a very advantageous spectrum ofactivities for protecting useful plants against diseases that are causedby phytopathogenic microorganisams, such as fungi, bacteria or viruses.

The invention therefore also relates to a method of controlling orpreventing infestation of useful plants by phytopathogenicmicroorganisms, wherein a compound of formula I is applied as activeingredient to the plants, to parts thereof or the locus thereof. Thecompounds of formula I according to the invention are distinguished byexcellent activity at low rates of application, by being well toleratedby plants and by being environmentally safe.

They have very useful curative, preventive and systemic properties andare used for protecting numerous useful plants. The compounds of formulaI can be used to inhibit or destroy the diseases that occur on plants orparts of plants (fruit, blossoms, leaves, stems, tubers, roots) ofdifferent crops of useful plants, while at the same time protecting alsothose parts of the plants that grow later e.g. from phytopathogenicmicroorganisms.

It is also possible to use compounds of formula I as dressing agents forthe treatment of plant propagation material, in particular of seeds(fruit, tubers, grains) and plant cuttings (e.g. rice), for theprotection against fungal infections as well as against phytopathogenicfungi occurring in the soil.

Furthermore the compounds of formula I according to the invention may beused for controlling fungi in related areas, for example in theprotection of technical materials, including wood and wood relatedtechnical products, in food storage or in hygiene management.

The compounds of formula I are, for example, effective against thephytopathogenic fungi of the following classes: Fungi imperfecti (e.g.Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercosporaand Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia,Puccinia). Additionally, they are also effective against the Ascomycetesclasses (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula)and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara).Outstanding activity has been observed against powdery mildew (Erysiphespp.). Furthermore, the novel compounds of formula I are effectiveagainst phytopathogenic bacteria and viruses (e.g. against Xanthomonasspp, Pseudomonas spp, Erwinia amylovora as well as against the tobaccomosaic virus). Good activity has been observed against Asian soybeanrust (Phakopsora pachyrhizi).

Within the scope of the invention, useful plants to be protectedtypically comprise the following species of plants: cereal (wheat,barley, rye, oat, rice, maize, sorghum and related species); beet (sugarbeet and fodder beet); pomes, drupes and soft fruit (apples, pears,plums, peaches, almonds, cherries, strawberries, raspberries andblackberries); leguminous plants (beans, lentils, peas, soybeans); oilplants (rape, mustard, poppy, olives, sunflowers, coconut, castor oilplants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers,melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges,lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus,cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae(avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee,eggplants, sugar cane, tea, pepper, vines, hops, bananas and naturalrubber plants, as well as ornamentals.

The term “useful plants” is to be understood as including also usefulplants that have been rendered tolerant to herbicides like bromoxynil orclasses of herbicides (such as, for example, HPPD inhibitors, ALSinhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron,EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS(glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase)inhibitors) as a result of conventional methods of breeding or geneticengineering. An example of a crop that has been rendered tolerant toimidazolinones, e.g. imazamox, by conventional methods of breeding(mutagenesis) is Clearfield® summer rape (Canola). Examples of cropsthat have been rendered tolerant to herbicides or classes of herbicidesby genetic engineering methods include glyphosate- andglufosinate-resistant maize varieties commercially available under thetrade names RoundupReady®, Herculex I® and LibertyLink®.

The term “useful plants” is to be understood as including also usefulplants which have been so transformed by the use of recombinant DNAtechniques that they are capable of synthesising one or more selectivelyacting toxins, such as are known, for example, from toxin-producingbacteria, especially those of the genus Bacillus.

Examples of such plants are: YieldGard® (maize variety that expresses aCryIA(b) toxin); YieldGard Rootworm® (maize variety that expresses aCryIIIB(b1) toxin); YieldGard Plus®(maize variety that expresses aCryIA(b) and a CryIIIB(b1) toxin); Starlink® (maize variety thatexpresses a Cry9(c) toxin); Herculex I® (maize variety that expresses aCryIF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase(PAT) to achieve tolerance to the herbicide glufosinate ammonium);NuCOTN 33B® (cotton variety that expresses a CryIA(c) toxin); BollgardI® (cotton variety that expresses a CryIA(c) toxin); Bollgard II®(cotton variety that expresses a CryIA(c) and a CryIIA(b) toxin);VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potatovariety that expresses a CryIIIA toxin); NatureGard® Agrisure® GTAdvantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11corn borer (CB) trait), Agrisure® RW (corn rootworm trait) andProtecta®.

The term “useful plants” is to be understood as including also usefulplants which have been so transformed by the use of recombinant DNAtechniques that they are capable of synthesising antipathogenicsubstances having a selective action, such as, for example, theso-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392225). Examples of such antipathogenic substances and transgenic plantscapable of synthesising such antipathogenic substances are known, forexample, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. Themethods of producing such transgenic plants are generally known to theperson skilled in the art and are described, for example, in thepublications mentioned above.

The term “locus” of a useful plant as used herein is intended to embracethe place on which the useful plants are growing, where the plantpropagation materials of the useful plants are sown or where the plantpropagation materials of the useful plants will be placed into the soil.An example for such a locus is a field, on which crop plants aregrowing.

The term “plant propagation material” is understood to denote generativeparts of the plant, such as seeds, which can be used for themultiplication of the latter, and vegetative material, such as cuttingsor tubers, for example potatoes. There may be mentioned for exampleseeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes andparts of plants. Germinated plants and young plants which are to betransplanted after germination or after emergence from the soil, mayalso be mentioned. These young plants may be protected beforetransplantation by a total or partial treatment by immersion. Preferably“plant propagation material” is understood to denote seeds.

The compounds of formula I can be used in unmodified form or,preferably, together with carriers and adjuvants conventionally employedin the art of formulation.

Therefore the invention also relates to compositions for controlling andprotecting against phytopathogenic microorganisms, comprising a compoundof formula I and an inert carrier, and to a method of controlling orpreventing infestation of useful plants by phytopathogenicmicroorganisms, wherein a composition, comprising a compound of formulaI as acitve ingredient and an inert carrier, is applied to the plants,to parts thereof or the locus thereof.

To this end compounds of formula I and inert carriers are convenientlyformulated in known manner to emulsifiable concentrates, coatablepastes, directly sprayable or dilutable solutions, dilute emulsions,wettable powders, soluble powders, dusts, granulates, and alsoencapsulations e.g. in polymeric substances. As with the type of thecompositions, the methods of application, such as spraying, atomising,dusting, scattering, coating or pouring, are chosen in accordance withthe intended objectives and the prevailing circumstances. Thecompositions may also contain further adjuvants such as stabilizers,antifoams, viscosity regulators, binders or tackifiers as well asfertilizers, micronutrient donors or other formulations for obtainingspecial effects.

Suitable carriers and adjuvants (auxiliaries) can be solid or liquid andare substances useful in formulation technology, e.g. natural orregenerated mineral substances, solvents, dispersants, wetting agents,tackifiers, thickeners, binders or fertilizers. Such carriers are forexample described in WO 97/33890.

The compounds of formula I or compositions, comprising a compound offormula I as active ingredient and an inert carrier, can be applied tothe locus of the plant or plant to be treated, simultaneously or insuccession with further compounds. These further compounds can be e.g.fertilizers or micronutrient donors or other preparations whichinfluence the growth of plants. They can also be selective herbicides aswell as insecticides, fungicides, bactericides, nematicides,molluscicides or mixtures of several of these preparations, if desiredtogether with further carriers, surfactants or application promotingadjuvants customarily employed in the art of formulation.

A preferred method of applying a compound of formula I, or acomposition, comprising a compound of formula I as active ingredient andan inert carrier, is foliar application. The frequency of applicationand the rate of application will depend on the risk of infestation bythe corresponding pathogen. However, the compounds of formula I can alsopenetrate the plant through the roots via the soil (systemic action) bydrenching the locus of the plant with a liquid formulation, or byapplying the compounds in solid form to the soil, e.g. in granular form(soil application). In crops of water rice such granulates can beapplied to the flooded rice field. The compounds of formula I may alsobe applied to seeds (coating) by impregnating the seeds or tubers eitherwith a liquid formulation of the fungicide or coating them with a solidformulation.

A formulation, i.e. a composition comprising the compound of formula Iand, if desired, a solid or liquid adjuvant, is prepared in a knownmanner, typically by intimately mixing and/or grinding the compound withextenders, for example solvents, solid carriers and, optionally,surface-active compounds (surfactants).

The agrochemical formulations will usually contain from 0.1 to 99% byweight, preferably from 0.1 to 95% by weight, of the compound of formulaI, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid orliquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25%by weight, of a surfactant.

Whereas it is preferred to formulate commercial products asconcentrates, the end user will normally use dilute formulations.

Advantageous rates of application are normally from 5 g to 2 kg ofactive ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kga.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seeddrenching agent, convenient rates of application are from 10 mg to 1 gof active substance per kg of seeds. The rate of application for thedesired action can be determined by experiments. It depends for exampleon the type of action, the developmental stage of the useful plant, andon the application (location, timing, application method) and can, owingto these parameters, vary within wide limits.

The compounds of formula (I), or a pharmaceutical salt thereof,described above may also have an advantageous spectrum of activity forthe treatment and/or prevention of microbial infection in an animal.“Animal” can be any animal, for example, insect, mammal, reptile, fish,amphibian, preferably mammal, most preferably human. “Treatment” meansthe use on an animal which has microbial infection in order to reduce orslow or stop the increase or spread of the infection, or to reduce theinfection or to cure the infection. “Prevention” means the use on ananimal which has no apparent signs of microbial infection in order toprevent any future infection, or to reduce or slow the increase orspread of any future infection. According to the present invention thereis provided the use of a compound of formula (I) in the manufacture of amedicament for use in the treatment and/or prevention of microbialinfection in an animal. There is also provided the use of a compound offormula (I) as a pharmaceutical agent. There is also provided the use ofa compound of formula (I) as an antimicrobial agent in the treatment ofan animal. According to the present invention there is also provided apharmaceutical composition comprising as an active ingredient a compoundof formula (I), or a pharmaceutically acceptable salt thereof, and apharmaceutically acceptable diluent or carrier. This composition can beused for the treatment and/or prevention of antimicrobial infection inan animal. This pharmaceutical composition can be in a form suitable fororal administration, such as tablet, lozenges, hard capsules, aqueoussuspensions, oily suspensions, emulsions dispersible powders,dispersible granules, syrups and elixirs. Alternatively thispharmaceutical composition can be in a form suitable for topicalapplication, such as a spray, a cream or lotion. Alternatively thispharmaceutical composition can be in a form suitable for parenteraladministration, for example injection. Alternatively this pharmaceuticalcomposition can be in inhalable form, such as an aerosol spray. Thecompounds of formula (I) may be effective against various microbialspecies able to cause a microbial infection in an animal. Examples ofsuch microbial species are those causing Aspergillosis such asAspergillus fumigatus, A. flavus, A. terrus, A. nidulans and A. niger,those causing Blastomycosis such as Blastomyces dermatitidis; thosecausing Candidiasis such as Candida albicans, C. glabrata, C.tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causingCoccidioidomycosis such as Coccidioides immitis; those causingCryptococcosis such as Cryptococcus neoformans; those causingHistoplasmosis such as Histoplasma capsulatum and those causingZygomycosis such as Absidia corymbifera, Rhizomucor pusillus andRhizopus arrhizus. Further examples are Fusarium Spp such as Fusariumoxysporum and Fusarium solani and Scedosporium Spp such as Scedosporiumapiospermum and Scedosporium prolificans. Still further examples areMicrosporum Spp, Trichophyton Spp, Epidermophyton Spp, Mucor Spp,Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp,Paracoccidioides Spp and Histoplasma Spp.

The following non-limiting Examples illustrate the above-describedinvention in greater detail without limiting it.

PREPARATORY EXAMPLES General Procedure for High Speed Synthesis ExampleP0 Preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylicacid methoxy-amide Derivatives of Formula Ib

Step I:

To a stirred solution of a ketone of formula IV (0.06 mmol), in aceticacid (500 μl) was added methoxyamine (4.7 mg). The reaction mixture wasstirred at 24° C. for 48 h under nitrogen to obtain the O-methyl-oximeof formula VI.

Step II:

To the O-methyl-oxime from step I, a suspension of sodiumcyanoborohydride (11.3 mg) in DCE (200 μl) was added portion wise. Thereaction mixture was stirred at 24° C. for 18 h under nitrogen. Most ofacetic acid was removed under a stream of nitrogen to affordO-methyl-N-hydroxylamine of formula II.

Step III:

To O-methyl-N-hydroxylamine, prepared as described in step II, NaOH 0.75molar (300 μl) and NaOH 2.0 molar (500 μl) were added. Followed by theaddition of the addition of3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (11.7 mg)dissolved in dichloromethane (300 μl). The reaction mixture was stirredat ambient temperature for 18 hours under nitrogen atmosphere. Thesolvent was removed under a stream of nitrogen, followed by addition ofacetic acid (200 μl), water (100 μl), DMA (200 μl) and acetonitrile (200μl). The crude 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acidmethoxyamides of formula I were directly submitted for LCChromatography.

Purification:

The following purification method was used:

LC1 oder Z (Filename Z) Standard_Long gradient

Method B

MS ZMD Mass Spectrometer from Waters (single quadrupole massspectrometer), ionization method: electrospray, polarity: positiveionization, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 3.00,source temperature (° C.) 150, desolvation temperature (° C.) 320, conegas flow (L/Hr) 50, desolvation gas flow (L/Hr) 400, mass range: 150 to800 Da. LC Alliance 2795 LC HPLC from Waters: quaternary pump, heatedcolumn compartment and diode-array detector. Column: Waters Atlantisdc18; length: 20 mm; internal diameter: 3 mm; particle size: 3 μm,temperature (° C.) 40, DAD wavelength range (nm): 200 to 500, solventgradient: A = 0.1% of formic acid in water and B: 0.1% of formic acid inacetonitrile. Time (min) A % B % Flow (ml/min) 0.0 80  20 1.7 5.0  0.0100 1.7 5.6  0.0 100 1.7 6.0 80  20 1.7

Example P1 Preparation of3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(7-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-methoxy-amide (Compound1.003)

To a stirred solution ofN-(7-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-O-methyl-hydroxylamine(0.60 g; 2.80 mmol), prepared as described in example P1b andtriethylamine (0.80 ml; 5.70 mmol) in dichloromethane (10 ml) undernitrogen at 15° C. was added dropwise3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.545 g; 2.80mmol) in dichloromethane (5 ml). The reaction mixture was stirred at 22°C. for 14 h under nitrogen. The mixture was poured in water andextracted three times with dichloromethane. Combined organics were driedover sodium sulfate and the solvent was removed in vacuo. The crude wassubject to flash chromatography (eluant: c-hexane/ethyl acetate 60:40)to afford 0.95 g (91% of theory) of3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(7-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-methoxy-amide as a yellowoil, that crystallized.

¹H NMR (400 MHz, CHLOROFORM-d): ppm 1.78-1.86 (m, 1H), 2.05-2.15 (m,2H), 2.17-2.23 (m, 1H), 2.71-2.77 (m, 1H), 2.81-2.89 (m, 1H), 3.47 (s,3H), 4.00 (s, 3H), 5.76-5.79 (m, 1H), 7.05-7.07 (d, 1H), 7.13-7.17 (dd,1H), 7.26 (t, J=55.0 Hz, 1H), 7.29-7.30 (dd, 1H), 7.91 (s, 1H).

MS (ZMD) 370/372 ([M+1]⁺); 392/394 ([M+23]⁺) 1.84 min.

a) Preparation of7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime

To a stirred solution of 7-chloro-1-tetralone CAS: 26673-32-5 (5.0 g;27.68 mmol) in methanol (55 ml) was added pyridine (2.87 ml; 34.05 mmol)followed by a portion wise addition of methoxyamine hydrochloride (2.84g; 34.05 mmol). The reaction mixture was stirred at 24° C. for 16 hunder nitrogen. Methanol was removed under reduced pressure, the residuepoured in water (300 ml) and 1N hydrochloric acid was added (100 ml).The solution was extracted with dichloromethane (3×150 ml). Combinedorganic layers were washed with water (300 ml) and dried over sodiumsulfate. The solvent was removed in vacuo to afford 6.22 g (100% oftheory) of crude 7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oximeas a brown oil.

¹H NMR (400 MHz, CHLOROFORM-d):

ppm 1.78-1.83 (m, 2H), 2.65-2.72 (m, 4H), 3.98 (s, 3H), 7.03-7.06 (d,1H), 7.17-7.20 (dd, 1H), 7.94 (s, 1H).

MS (ZMD) 210/212 ([M+1]⁺) 1.89 min.

b) Preparation ofN-(7-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-O-methyl-hydroxylamine

To a stirred solution of crude7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime (5.9 g; 28.14mmol) prepared as described in example P1a in acetic acid (100 ml) wasadded portion wise sodium cyanoborohydride 95% (3.54 g; 56.3 mmol) at15° C. The mixture was stirred for 6 hours at 23° C. Most of acetic acidwas removed under reduced pressure. The residue was poured in 2N NaOH(100 ml) and was extracted with ethylacetate (3×80 ml).

Combined organics were dried over sodium sulfate and solvent was removedin vacuo. The crude (8.2 g) was subject to flash chromatography (eluant:c-hexane/ethyl acetate 90:10) to afford 2.70 g (45% of theory) ofN-(7-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-O-methyl-hydroxylamineas a yellow oil.

¹H NMR (400 MHz, CHLOROFORM-d):

ppm 1.71-2.13 (m, 4H), 2.62-2.83 (m, 2H), 3.56 (s, 3H), 4.08-4.11 (t,1H), 5.50 (s_(br), 1 NH), 7.01-7.03 (d, 1H), 7.38-7.39 (dd, 1H).

MS (ZMD) 212/214 ([M+1]⁺) 1.75 min.

Example P2 Preparation of3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(6-fluoro-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-methoxy-amide(Compound 1.065)

To a stirred solution ofN-(6-fluoro-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylamine(0.100 g; 0.48 mmol), prepared as described in example P2b andtriethylamine (0.073 ml; 0.53 mmol) in dichloromethane (1 ml) undernitrogen at 0° C. was added drop wise3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.093 g; 0.48mmol). The reaction mixture was stirred at 20° C. for 15 h undernitrogen. The solvent was removed in vacuo to afford a sticky oil whichwas subject to flash chromatography (eluant: c-hexane/ethyl acetate 95:5to 0:100) to afford 0.134 g (76% of theory) of3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(6-fluoro-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-methoxy-amide asan oil.

a) Preparation of6-fluoro-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oxime

To a stirred suspension of6-fluoro-6,7,8,9-tetrahydrobenzocylohepten-5-one CAS: 127053-30-9 (1.06g; 5.95 mmol) in methanol (12 ml) was added pyridine (1.53 ml; 19.04mmol) followed by a portionwise addition of methoxyamine hydrochloride(1.59 g; 19.04 mmol). The reaction mixture was stirred at 20° C. for 16h under nitrogen. The solvent was removed in vacuo to afford 1.28 g(100% of theory) of crude6-fluoro-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oximeE/Z-mixture as a brown oil.

MS (ZMD) 208 ([M+1]⁺) 1.74 min. and 1.80 min.

b) Preparation ofN-(6-fluoro-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylamine(Compound 4.065)

To a stirred solution of crude6-fluoro-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oximeE/Z-mixture (1.23 g; 5.95 mmol) prepared as described in example P2a inacetic acid (12 ml) was added portion wise sodium cyanoborohydride 95%(0.75 g; 11.9 mmol) at 15° C. The mixture was stirred for 6 hours at 23°C. Most of acetic acid was removed under reduced pressure. The residuewas poured in 2N NaOH (50 ml) and was extracted with ethylacetate (3×30ml). Combined organics were dried over sodium sulfate and solvent wasremoved in vacuo. The crude (1.45 g) was subject to flash chromatography(eluant: c-hexane/ethyl acetate 100:0 to 0:100) to afford 0.645 g (52%of theory) ofN-(6-fluoro-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylamineas a yellow oil.

MS (ZMD) 210 ([M+1]⁺) 1.67 min. and 1.70 min. both diastereomeres.

Example P3 Preparation of3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(3-iodo-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-methoxy-amide(Compound 1.062)

To a stirred solution ofN-(3-iodo-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylamine(77 mg; 0.24 mmol), prepared as described in example P3c andtriethylamine (0.037 ml; 0.26 mmol) in dichloromethane (1.6 ml) undernitrogen at 4° C. was added dropwise1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (47 mg; 0.24mmol). The reaction mixture was stirred at 24° C. for 3 h undernitrogen. The mixture diluted with dichloromethane (10 ml), washed with1M sodium hydroxide (1 ml), 1M hydrochloric acid (1 ml) and brine (1ml). Organics were dried over sodium sulfate. The solvent was removed invacuo. The crude (190 mg) was subject to flash chromatography (eluant:c-hexane/ethyl acetate 90:10 to 50:50) to afford 0.101 g (88% of theory)of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid(3-iodo-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-methoxy-amide as ayellow solid oil.

MS (ZMD) 476 ([M+1]⁺) 1.93 min.

a) Preparation of 3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one

To a stirred solution of p-TsOH monohydrate (1.72 g; 9.0 mmol) inacetonitrile (12 ml) was added 3-aminobenzosuberone CAS: 95207-68-4(0.526 g; 3.0 mmol). To the resulting pale brown solution a solution ofsodium nitrite (414 mg; 6.0 mmol) and potassium iodide (1.25 g; 7.5mmol) in water (1.8 ml) was added at 10-15° C. The mixture was stirredfor 10 minutes at 15° C. and an additional 1.5 hours at 20° C. Thereaction mixture was poured onto water (50 ml), adjusted to pH 8-10 bythe addition of 1M NaHCO₃ solution and decolorized by the addition ofNa₂S₂O₃ solution. The aqueous was extracted with ethyl acetate (3×30ml). Combined organics were dried over sodium sulfate and solvent wasremoved in vacuo to afford 850 mg (99% of theory) of pure3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one as an oil.

MS (ZMD) 287 ([M+1]⁺) 1.85 min.

b) Preparation of3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oxime

To a stirred suspension of3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one prepared as described inexample P3a (0.806 g; 2.82 mmol) in methanol (5.7 ml) was added pyridine(0.7 ml; 9.02 mmol) followed by a portion wise addition of methoxyaminehydrochloride (0.754 g; 9.02 mmol). The reaction mixture was stirred at20° C. for 16 h under nitrogen. The solvent was removed in vacuo toafford 0.86 g (97% of theory) of crude3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oximeE/Z-mixture as a brown oil.

MS (ZMD) 316 ([M+1]⁺) 2.01 min. and 2.12 min.

c) Preparation ofN-(3-iodo-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylamine

To a stirred solution of crude3-iodo-6,7,8,9-tetrahydrobenzocylohepten-5-one-O-methyl-oximeE/Z-mixture (793 mg; 5.95 mmol) prepared as described in example P3b inacetic acid (5 ml) was added portion wise sodium cyanoborohydride 95%(0.63 g; 10.1 mmol) at 15° C. The mixture was stirred for 9 hours at 23°C. Most of acetic acid was removed under reduced pressure. The residuewas poured in 2N NaOH (50 ml) and was extracted with ethylacetate (3×30ml). Combined organics were dried over sodium sulfate and solvent wasremoved in vacuo. The crude (840 mg) was subject to flash chromatography(eluant: c-hexane/ethyl acetate 100:0 to 10:90) to afford 88 mg (13% oftheory) ofN-(3-iodo-6,7,8,9-tetrahydro-5-H-benzocyclohepten-5-yl)-O-methyl-hydroxylaminein form of an oil.

MS (ZMD) 318 ([M+1]⁺) 2.12 min.

Tables 1 to 3 and 5: Compounds of Formula Ia:

The invention was further illustrated by the preferred individualcompounds of formula (Ia) listed below in Tables 1 to 3 and 5.Characterising data are given in Table 6.

In the compounds of formula Ia, A is selected from the groups consistingof A₁,

Each of Tables 1 to 5, which follow the Table Y below, comprises 79compounds of the formula (Ia) and (II) respectively, in which R₄, R₅,R₆, R₇, R₈, R₉, R₁₀, X and n have the values given in Table Y and A hasthe value given in the relevant Table 1 to 5.

In Tables 1 to 5 below “Me” signifies methyl, “c-Prop” signifiescyclopropyl and “t-Bu” signifies tertiary butyl.

TABLE Y Cpd No. R₄ R₅ R₆ R₇ R₈ R₉ R₁₀ n X Y.001 Me H H H H H H 1 CH₂Y.002 Me H H Cl H H H 1 CH₂ Y.003 Me H H H Cl H H 1 CH₂ Y.004 Me H H H HCl H 1 CH₂ Y.005 Me H H H H H Cl 1 CH₂ Y.006 Me F H H H H H 1 CH₂ Y.007Me F H Cl H H H 1 CH₂ Y.008 Me F H H Cl H H 1 CH₂ Y.009 Me F H H H Cl H1 CH₂ Y.010 Me F H H H H Cl 1 CH₂ Y.011 Me Me H H H H H 1 CH₂ Y.012 MeMe H Cl H H H 1 CH₂ Y.013 Me Me H H Cl H H 1 CH₂ Y.014 Me Me H H H Cl H1 CH₂ Y.015 Me Me H H H H Cl 1 CH₂ Y.016 Me Me Me H H H H 1 CH₂ Y.017 MeH H OMe H H H 1 CH₂ Y.018 Me H H H OMe H H 1 CH₂ Y.019 Me H H H H OMe H1 CH₂ Y.020 Me H H H H H OMe 1 CH₂ Y.021 Me H H F H H H 1 CH₂ Y.022 Me HH H F H H 1 CH₂ Y.023 Me H H H H F H 1 CH₂ Y.024 Me H H H H H F 1 CH₂Y.025 Me H H Me H H H 1 CH₂ Y.026 Me H H H Me H H 1 CH₂ Y.027 Me H H H HMe H 1 CH₂ Y.028 Me H H H H H Me 1 CH₂ Y.029 Me H H Me Me H H 1 CH₂Y.030 Me H H Me H Me H 1 CH₂ Y.031 Me H H Me H H Me 1 CH₂ Y.032 Me H H HMe Me H 1 CH₂ Y.033 Me H H H Me H Me 1 CH₂ Y.034 Me H H H H Me Me 1 CH₂Y.035 Me H H Cl Cl H H 1 CH₂ Y.036 Me H H Cl H Cl H 1 CH₂ Y.037 Me H HCl H H Cl 1 CH₂ Y.038 Me H H H Cl Cl H 1 CH₂ Y.039 Me H H H Cl H Cl 1CH₂ Y.040 Me H H H H Cl Cl 1 CH₂ Y.041 Me H H H H H H 1 O Y.042 Me H HCl H H H 1 O Y.043 Me H H H Cl H H 1 O Y.044 Me H H H H Cl H 1 O Y.045Me H H H H H Cl 1 O Y.046 Me H H F H H H 1 O Y.047 Me H H H F H H 1 OY.048 Me H H H H F H 1 O Y.049 Me H H H H H F 1 O Y.050 Me H H H H H H 1S Y.051 Me H H Cl H H H 1 S Y.052 Me H H H Cl H H 1 S Y.053 Me H H H HCl H 1 S Y.054 Me H H H H H Cl 1 S Y.055 Me H H H H H H 2 CH₂ Y.056 Me HH Cl H H H 2 CH₂ Y.057 Me H H H Cl H H 2 CH₂ Y.058 Me H H H H Cl H 2 CH₂Y.059 Me H H H H H Cl 2 CH₂ Y.060 Me H H H H H H 2 CH₂ Y.061 Me H H I HH H 2 CH₂ Y.062 Me H H H I H H 2 CH₂ Y.063 Me H H H H I H 2 CH₂ Y.064 MeH H H H H I 2 CH₂ Y.065 Me F H H H H H 2 CH₂ Y.066 Me F H Cl H H H 2 CH₂Y.067 Me F H H Cl H H 2 CH₂ Y.068 Me F H H H Cl H 2 CH₂ Y.069 Me F H H HH Cl 2 CH₂ Y.070 Me H H H NH₂ H H 2 CH₂ Y.071 Me H H H NHC(O)Ot-Bu H H 2CH₂ Y.072 Me H H H NHC(O)Me H H 2 CH₂ Y.073 Me H H H NHC(O)c-Prop H H 2CH₂ Y.074 Me Me H Cl Cl H H 2 CH₂ Y.075 Me Me H Cl H Cl H 2 CH₂ Y.076 MeMe H Cl H H Cl 2 CH₂ Y.077 Me Me H H Cl Cl H 2 CH₂ Y.078 Me Me H H Cl HCl 2 CH₂ Y.079 Me Me H H H Cl Cl 2 CH₂

Table 1 provides 79 compounds of formula (Ia), wherein A is A₁

and R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, X and n are as defined in Table Y.

For example, compound 1.001 has the following structure:

Table 2 provides 79 compounds of formula (Ia), wherein A is A₂

and R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, X and n are as defined in Table Y.

For example, compound 2.067 has the following structure:

Table 3 provides 79 compounds of formula (Ia), wherein A is A₃

and R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, X and n are as defined in Table Y.

For example, compound 3.071 has the following structure:

Table 4:

Table 4 provides 79 compounds of formula (II)

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, X and n are as defined in Table Y.

For example, compound 4.065 has the following structure:

Table 5:

Table 5 provides 79 compounds of formula (Ia), wherein A is A₄

and R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, X and n are as defined in Table Y.

Table 6: Characterisinq Data:

Table 6 shows selected melting point and selected NMR data for compoundsof Table 1 to 3. CDCl₃ is used as the solvent for NMR measurements,unless otherwise stated. If a mixture of solvents is present, this isindicated as, for example: CDCl₃/d₆-DMSO). No attempt is made to listall characterising data in all cases.

In Table 6 and throughout the description that follows, temperatures aregiven in degrees Celsius; “NMR” means nuclear magnetic resonancespectrum; MS signifies mass spectrum; “%” is percent by weight, unlesscorresponding concentrations are indicated in other units. The followingabbreviations are used throughout this description:

m.p. = melting point b.p. = boiling point. S = singlet br = broad d =doublet dd = doublet of doublets t = triplet q = quartet m = multipletppm = parts per million

Method for GC-MS Volatile CI/EI

Mass spectra were obtained with GC-MS was conducted on a Thermo, MS: DSQand GC: TRACE GC ULTRA with a column from Zebron phenomenex: Phase ZB-5ms 15 m, diam: 0.25 mm, 0.25 μm, H₂ flow 1.7 mL/min, temp injector: 250°C., temp detector: 220° C., method: hold 2 min at 40° C., 25° C./minuntil 320° C., hold 1 min 12 s at 320° C., total time 15 min. All otherreagents and solvents, unless otherwise noted, were purchased fromcommercial vendors and used without further purification.

Method for LC-MS Method C

MS ZQ Mass Spectrometer from Waters (single quadrupole massspectrometer), ionization method: electrospray, polarity: positiveionization, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 3.00,source temperature (° C.) 100, desolvation temperature (° C.) 200, conegas flow (L/Hr) 200, desolvation gas flow (L/Hr) 250, mass range: 150 to800 Da. LC 1100er Series HPLC from Agilent: quaternary pump, heatedcolumn compartment and diode-array detector. Column: Waters Atlantisdc18; length: 20 mm; internal diameter: 3 mm; particle size: 3 μm,temperature (° C.) 40, DAD wavelength range (nm): 200 to 500, solventgradient: A = 0.1% of formic acid in water and B: 0.1% of formic acid inacetonitrile. Time (min) A % B % Flow (ml/min) 0.0 90  10 1.7 5.5  0.0100 1.7 5.8  0.0 100 1.7 5.9 90  10 1.7

TABLE 6 Cpd 1H-NMR data: ppm MS [M + H]⁺ m.p. No. (multiplicity/numberof Hs) ZMD (° C.) LCMS data 1.001 336 ([M + 1]⁺) 1.81 min. 91-95 1.0031.78-1.86 (m, 1 H), 2.05-2.15 (m, 2 370/372 ([M + 1]⁺); H), 2.17-2.23(m, 1 H), 2.71-2.77 (m, 392/394 ([M + 23]⁺) 1.84 min. 1H), 2.81-2.89 (m,1H), 3.47 (s, 3 H), 4.00 (s, 3 H), 5.76-5.79 (m, 1 H), 7.05-7.07 (d, 1H), 7.13-7.17 (dd, 1H), 7.26 (t, J = 55.0 Hz, 1 H), 7.29-7.30 (dd, 1 H),7.91 (s, 1 H) 1.011 3.06 (350.14) 1.016 368 ([M + 23]⁺) 114-118 1.92min. 1.018 388 ([M + 23]⁺) liquid 1.76 min. 1.019 388 ([M + 23]⁺) liquid1.74 min. 1.020 2.96 (366.10) 1.033 3.32 (364.15) 1.041 2.37 (338.13)1.043 2.88 (372.02) 1.045 2.81 (372.02) 1.047 2.62 (356.06) 1.050 2.68(354.04) 1.055 1.43-2.29 (m, 6 H), 2.75-2.85 (m, 1 350 ([M + 1]⁺) 1.84min. 123-127 H), 2.91-3.01 (m, 1 H), 3.63 (s, 3 H), 3.98 (s, 3 H),5.68-5.71 (m, 1 H), 7.09-7.18 (m, 3 H), 7.20-7.23 (m, 1H), 7.28 (t, J =55.0 Hz, 1 H), 7.29-7.30 (dd, 1 H), 7.98 (s, 1 H) 1.057 384/386 ([M +1]⁺); 51-55 406/408 ([M + 23]⁺) 1.91 min. 1.058 384/386 ([M + 1]⁺);127-131 1.96 min. 1.059 384/386 ([M + 1]⁺); 125-127 406/408 ([M + 23]⁺)1.92 min. 1.062 476 ([M + 1]⁺) 1.93 min. oil 1.065 368 ([M + 1]⁺);liquid 381 ([M + 23]⁺) 1.79 min. 1.067 402 ([M + 1]⁺); liquid 424 ([M +23]⁺) 1.90 min. 1.070 365 ([M + 1]⁺); 119-123 387 ([M + 23]⁺) 1.31 min.1.071 465 ([M + 1]⁺); 190-193 487 ([M + 23]⁺) 1.96 min. 1.072 407 ([M +1]⁺); 218-222 429 ([M + 23]⁺) 1.62 min. 1.073 433 ([M + 1]⁺); 189-191455 ([M + 23]⁺) 1.62 min.

Formulation Examples for Compounds of Formula I Example F-1.1 to F-1.2Emulsifiable Concentrates

Components F-1.1 F-1.2 compound of Tables 1-3, 5 25% 50% calciumdodecylbenzenesulfonate  5%  6% castor oil polyethylene glycol ether  5%— (36 mol ethylenoxy units) tributylphenolpolyethylene glycol ether — 4% (30 mol ethylenoxy units) cyclohexanone — 20% xylene mixture 65% 20%

Emulsions of any desired concentration can be prepared by diluting suchconcentrates with water.

Example F-2 Emulsifiable Concentrate

Components F-2 compound of Tables 1-3, 5 10% octylphenolpolyethyleneglycol ether 3% (4 to 5 mol ethylenoxy units) calciumdodecylbenzenesulfonate 3% castor oil polyglycol ether 4% (36 molethylenoxy units) cyclohexanone 30% xylene mixture 50%

Emulsions of any desired concentration can be prepared by diluting suchconcentrates with water.

Examples F-3.1 to F-3.4 Solutions

Components F-3.1 F-3.2 F-3.3 F-3.4 compound of Tables 1-3, 5 80% 10% 5%95% propylene glycol monomethyl ether 20% — — — polyethylene glycol(relative molecular — 70% — — mass: 400 atomic mass units)N-methylpyrrolid-2-one — 20% — — epoxidised coconut oil — — 1%  5%benzin (boiling range: 160-190°) — — 94%  —

The solutions are suitable for use in the form of microdrops.

Examples F-4.1 to F-4.4 Granulates

Components F-4.1 F-4.2 F-4.3 F-4.4 compound of Tables 1-3, 5 5% 10%  8%21% kaolin 94%  — 79% 54% highly dispersed silicic acid 1% — 13% 7%attapulgite — 90% — 18%

The novel compound is dissolved in dichloromethane, the solution issprayed onto the carrier and the solvent is then removed by distillationunder vacuum.

Examples F-5.1 and F-5.2 Dusts

Components F-5.1 F-5.2 compound of Tables 1-3, 5 2% 5% highly dispersedsilicic acid 1% 5% talcum 97%  — kaolin — 90% 

Ready for use dusts are obtained by intimately mixing all components.

Examples F-6.1 to F-6.3 Wettable Powders

Components F-6.1 F-6.2 F-6.3 compound of Tables 1-3, 5 25%  50% 75%sodium lignin sulfonate 5%  5% — sodium lauryl sulfate 3% —  5% sodiumdiisobutylnaphthalene —  6% 10% sulfonate octylphenolpolyethylene glycolether —  2% — (7 to 8 mol ethylenoxy units) highly dispersed silicicacid 5% 10% 10% kaolin 62%  27% —

All components are mixed and the mixture is thoroughly ground in asuitable mill to give wettable powders which can be diluted with waterto suspensions of any desired concentration.

Example F7 Flowable Concentrate for Seed Treatment

compound of Tables 1-3, 5 40%  propylene glycol 5% copolymer butanolPO/EO 2% tristyrenephenole with 10-20 moles EO 2%1,2-benzisothiazolin-3-one (in the form of a 0.5%   20% solution inwater) monoazo-pigment calcium salt 5% Silicone oil (in the form of a75% emulsion 0.2%   in water) Water 45.3%  

The finely ground active ingredient is intimately mixed with theadjuvants, giving a suspension concentrate from which suspensions of anydesired dilution can be obtained by dilution with water. Using suchdilutions, living plants as well as plant propagation material can betreated and protected against infestation by microorganisms, byspraying, pouring or immersion.

Biological Examples Fungicidal Action Example B-1 Action AgainstBotrytis cinerea—Fungal Growth Assay

Conidia of the fungus from cryogenic storage was directly mixed intonutrient broth (PDB potato dextrose broth). After placing a (DMSO)solution of the test compounds (0.002% active ingredient) into amicrotiter plate (96-well format) the nutrient broth containing thefungal spores was added. The test plates were incubated at 24° C. andthe inhibition of growth was measured photometrically after 3-4 days.The activity of a compound was expressed as fungal growth inhibition(0=no growth inhibition, ratings of 80% to 99% mean good to very goodinhibition, 100%=complete inhibition).

Compounds 1.001, 1.020, 1.030, 1.033, 1.055, 1.057, 1.059 and 1.065 showvery good activity in this test (≧80% inhibition).

Example B-2 Action Against Mycosphaerella arachidis (Early Leaf Spot ofGroundnut; Cercospora arachidicola [anamorph])—Fungal Growth Assay

Conidia of the fungus from cryogenic storage were directly mixed intonutrient broth (Pdb potato dextrose broth). After placing a (DMSO)solution of the test compounds (0.002% active ingredient) into amicrotiter plate (96-well format) the nutrient broth containing thefungal spores was added. The test plates were incubated at 24° C. andthe inhibition of growth was measured photometrically after 6-7 days.The activity of a compound was expressed as fungal growth inhibition(0=no growth inhibition, ratings of 80% to 99% mean good to very goodinhibition, 100%=complete inhibition).

Compounds 1.001, 1.003, 1.011, 1.016, 1.018, 1.019, 1.020, 1.030, 1.033,1.041, 1.043, 1.045, 1.047, 1.050, 1.055, 1.057, 1.058, 1.059, 1.062,1.065, 1.067, 1.071 and 1.072 show very good activity in this test (≧80%inhibition).

Example B-3 Action Against Septoria tritici—Fungal Growth Assay

Conidia of the fungus from cryogenic storage were directly mixed intonutrient broth (PDB potato dextrose broth). After placing a (DMSO)solution of the test compounds (0.002% active ingredient) into amicrotiter plate (96-well format) the nutrient broth containing thefungal spores was added. The test plates were incubated at 24° C. andthe inhibition of growth was determined photometrically after 72 hrs.The activity of a compound was expressed as fungal growth inhibition(0=no growth inhibition, ratings of 80% to 99% mean good to very goodinhibition, 100%=complete inhibition).

Compounds 1.001, 1.003, 1.011, 1.016, 1.018, 1.019, 1.020, 1.030, 1.033,1.041, 1.043, 1.045, 1.047, 1.050, 1.055, 1.057, 1.058, 1.059, 1.062,1.065, 1.067, 1.071 and 1.072 show very good activity in this test (≧80%inhibition).

Example B-4 Action Against Erysiphe graminis f. sp. tritici (WheatPowdery Mildew)

Wheat leaf segments were placed on agar in multiwell plates (24-wellformat) and sprayed with test solutions (0.02% active ingredient). Afterdrying, the leaf disks were inoculated with a spore suspension of thefungus. After appropriate incubation the activity of a compound wasassessed 7 days after inoculation as preventive fungicidal activity.

Compounds 1.001, 1.003, 1.011, 1.018, 1.019, 1.030, 1.033, 1.041, 1.043,1.045, 1.047, 1.055, 1.057, 1.058, 1.059, 1.065, and 1.067 show verygood activity in this test (≧80% inhibition).

Example B-5 Protective Action Against Puccinia recondita (Brown Rust) onWheat

Wheat leaf segments were placed on agar in multiwell plates (24-wellformat) and sprayed with test solutions (0.02% active ingredient). Afterdrying, the leaf disks were inoculated with a spore suspension of thefungus. After appropriate incubation the activity of a compound wasassessed 8 days after inoculation as preventive fungicidal activity.

Compounds 1.001, 1.003, 1.011, 1.018, 1.019, 1.020, 1.030, 1.033, 1.043,1.050, 1.055, 1.057, 1.058, 1.059, 1.062, 1.065, 1.067, 1.070 and 1.071show very good activity in this test (≧80% inhibition).

Example B-6 Curative Action Against Puccinia recondita (Brown Rust) onWheat

Wheat leaf segments were placed on agar in multiwell plates (24-wellformat) and inoculated with a spore suspension of the fungus. One dayafter inoculation the leaf segments were sprayed with test solutions(0.02% active ingredient). After appropriate incubation the activity ofa compound was assessed 8 days after inoculation as curative fungicidalactivity.

Compounds 1.001, 1.003, 1.011, 1.018, 1.019, 1.030, 1.041, 1.043, 1.047,1.055, 1.057, 1.058, 1.059, 1.062, 1.065, 1.067 and 1.071 show very goodactivity in this test (≧80% inhibition).

Example B-7 Action Against Pyrenophora teres (Net Blotch) on Barley

Barley leaf segments were placed on agar in multiwell plates (24-wellformat) and sprayed with test solutions (0.02% active ingredient). Afterdrying, the leaf disks were inoculated with a spore suspension of thefungus. After appropriate incubation the activity of a compound wasassessed 4 days after inoculation as preventive fungicidal activity.

Compounds 1.001, 1.003, 1.011, 1.018, 1.019, 1.020, 1.030, 1.041, 1.045,1.055, 1.057, 1.058, 1.059, 1.065, 1.067 and 1.072 show very goodactivity in this test (≧80% inhibition).

What is claimed is:
 1. A compound of formula I

wherein R₁ is C₁-C₄alkyl, C₁-C₄haloalkyl or C₁-C₄alkoxy; R₂ isC₁-C₄alkyl; R₃ is hydrogen or halogen; R₄ is hydrogen, C₁-C₄alkyl orC₁-C₄halogenalkyl; R₅ is hydrogen, halogen or C₁-C₄alkyl; R₆ ishydrogen, halogen, C₁-C₄alkyl, C₂-C₆alkenyl or C₃-C₆alkynyl; R₇ ishydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl, C₃-C₆alkynyl,C₃-C₆cycloalkyl-C₃-C₆alkynyl, C₁-C₆haloalkyl, C₁-C₆haloalkoxy,C₂-C₆haloalkenyl, or C₂-C₆haloalkenyloxy; R₈ is hydrogen, halogen,C₁-C₄alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl, C₃-C₆alkynyl, amino,C₁-C₆alkylcarbonylamino, C₁-C₆alkoxycarbonylamino orC₃-C₆cycloalkylcarbonylamino; R₉ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl, C₃-C₆alkynyl, C₃-C₆cycloalkyl-C₃-C₆alkynyl,halophenoxy, halophenyl, C₁-C₆haloalkyl, C₁-C₆haloalkoxy,C₂-C₆haloalkenyl, or C₂-C₆haloalkenyloxy; R₁₀ is hydrogen, halogen,C₁-C₄alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl or C₃-C₆alkynyl; X is CH₂, O or S;n is 0, 1 or 2; and agronomically acceptable salts/isomers/structuralisomers/stereoisomers/diastereoisomers/enantiomers/tautomers andN-oxides of those compounds.
 2. A compound of formula I according toclaim 1, wherein R₁ is difluoromethyl or trifluoromethyl; R₂ is methyl;R₃ is hydrogen; R₄ is methyl; R₆ is hydrogen, halogen, C₁-C₄alkyl,C₂-C₆alkenyl or C₃-C₆alkynyl; R₇, R₈, R₉ and R₁₀ are, independently fromeach other, hydrogen or halogen, preferably hydrogen or chloro.
 3. Acompound of formula I according to claim 1, wherein R₆ is hydrogen.
 4. Acompound of formula I according to claim 2, wherein R₆ is hydrogen.
 5. Acompound of formula I according to claim 1, wherein R₁ isdifluoromethyl, trifluoromethyl or methyl, R₂ is methyl; R₃ is hydrogen;R₄ is methyl; R₅ is hydrogen, fluoro or methyl; preferably hydrogen orfluoro; R₆ is hydrogen, halogen, C₁-C₄alkyl, C₂-C₆alkenyl orC₃-C₆alkynyl; n is 2; X is CH₂; and R₇, R₈, R₉ and R₁₀ are,independently from each other, hydrogen or halogen.
 6. A compound offormula I according to claim 5, wherein R₆ is hydrogen.
 7. A compound offormula I according to claim 1, wherein R₁ is C₁-C₄haloalkyl; R₂ isC₁-C₄alkyl; R₃ is hydrogen; R₄ is C₁-C₄alkyl; R₅ is hydrogen orC₁-C₄alkyl; R₆ is hydrogen or C₁-C₄alkyl; R₇ is hydrogen; R₈ ishydrogen, halogen, C₁-C₄alkyl, C₁-C₆alkoxy, amino,C₁-C₆alkylcarbonylamino, C₁-C₆alkoxycarbonylamino orC₃-C₆cycloalkylcarbonylamino; R₉ is hydrogen, halogen or C₁-C₆alkoxy;R₁₀ is hydrogen, halogen or C₁-C₆alkoxy; X is CH₂, O or S; and n is 1 or2.
 8. A compound of formula II

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, n and X are as defined underformula I in claim
 1. 9. A method of controlling or preventinginfestation of useful plants by phytopathogenic microorganisms, whereina compound of formula I according to claim 1 or a composition,comprising this compound as active ingredient, is applied to the plants,to parts thereof or the locus thereof.
 10. A composition for controllingand protecting against phytopathogenic microorganisms, comprising acompound of formula I according to claim 1 and at least one auxiliary.